Journal of Pathology and Translational Medicine

Case Study

Morule-like features in pulmonary adenocarcinoma associated with epidermal growth factor receptor mutations: two case reports with targeted next-generation sequencing analysis: Yoo Jin Lee, Harim Oh, Eojin Kim, Bokyung Ahn, Jeong Hyeon Lee, Youngseok Lee, Yang Seok Chae, Chul Hwan Kim; J Pathol Transl Med. 2020;54(1):119-122. Published online November 1, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.30

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Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.

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Pulmonary adenocarcinoma in situ with morule - like components: A surgical case report
Mitsuteru Yosida, Mitsuru Tomita, Naoya Kawakita, Teruki Shimizu, Ryou Yamada, Hiromitsu Takizawa, Hisanori Uehara
Respiratory Medicine Case Reports.2024; 48: 102008. CrossRef
Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components
Li-Li Wang, Li Ding, Peng Zhao, Jing-Jing Guan, Xiao-Bin Ji, Xiao-Li Zhou, Shi-Hong Shao, Yu-Wei Zou, Wei-Wei Fu, Dong-Liang Lin, Dong Pan
Disease Markers.2021; 2021: 1. CrossRef

Brief Case Report

Adenocarcinoma Arising in an Ectopic Hamartomatous Thymoma with HER2 Overexpression: Harim Oh, Eojin Kim, Bokyung Ahn, Jeong Hyeon Lee, Youngseok Lee, Yang Seok Chae, Chul Hwan Kim, Yoo Jin Lee; J Pathol Transl Med. 2019;53(6):403-406. Published online August 19, 2019; DOI: https://doi.org/10.4132/jptm.2019.06.23

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Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression
Martina Bradová, Lester D. R. Thompson, Martin Hyrcza, Tomáš Vaněček, Petr Grossman, Michael Michal, Veronika Hájková, Touraj Taheri, Niels Rupp, David Suster, Sunil Lakhani, Dimitar Hadži Nikolov, Radim Žalud, Alena Skálová, Michal Michal, Abbas Agaimy
Virchows Archiv.2024; 484(1): 103. CrossRef
Adenocarcinoma arising in branchioma with a KRAS and TP53 mutation
Natsuki Taniguchi, Akira Satou, Takanori Ito, Masato Nakaguro, Toyonori Tsuzuki
Pathology International.2023; 73(7): 317. CrossRef
Two Ectopic Hamartomatous Thymomas of Suprasternal Region of the Neck in A Single Patient: A Case Report
Wei WANG, Manmei LONG, Zhichao WANG
Chinese Journal of Plastic and Reconstructive Surgery.2021; 3(1): 51. CrossRef

Original Article

Morphometric Analysis of Thyroid Follicular Cells with Atypia of Undetermined Significance: Youngjin Kang, Yoo Jin Lee, Jiyoon Jung, Youngseok Lee, Nam Hee Won, Yang Seok Chae; J Pathol Transl Med. 2016;50(4):287-293. Published online June 13, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.04

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Abstract PDF

Background
Atypia of undetermined significance (AUS) is a category that encompasses a heterogeneous group of thyroid aspiration cytology. It has been reclassified into two subgroups based on the cytomorphologic features: AUS with cytologic atypia and AUS with architectural atypia. The nuclear characteristics of AUS with cytologic atypia need to be clarified by comparing to those observed in Hashimoto thyroiditis and benign follicular lesions.
Methods
We selected 84 cases of AUS with histologic follow-up, 24 cases of Hashimoto thyroiditis, and 26 cases of benign follicular lesions. We also subcategorized the AUS group according to the follow-up biopsy results into a papillary carcinoma group and a nodular hyperplasia group. The differences in morphometric parameters, including the nuclear areas and perimeters, were compared between these groups.
Results
The AUS group had significantly smaller nuclear areas than the Hashimoto thyroiditis group, but the nuclear perimeters were not statistically different. The AUS group also had significantly smaller nuclear areas than the benign follicular lesion group; however, the AUS group had significantly longer nuclear perimeters. The nuclear areas in the papillary carcinoma group were significantly smaller than those in the nodular hyperplasia group; however, the nuclear perimeters were not statistically different.
Conclusions
We found the AUS group to be a heterogeneous entity, including histologic follow-up diagnoses of papillary carcinoma and nodular hyperplasia. The AUS group showed significantly greater nuclear irregularities than the other two groups. Utilizing these features, nuclear morphometry could lead to improvements in the accuracy of the subjective diagnoses made with thyroid aspiration cytology.

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Meta-analysis on the utility of morphometry in the cytological differential diagnosis of thyroid neoplasms
Prema Saldanha
MGM Journal of Medical Sciences.2024; 11(1): 49. CrossRef
Gray zone Bethesda category III – Atypia of undetermined significance lesions of the thyroid: Potential diagnostic issues and image morphometry as a useful adjunct to cytomorphology
Tarunpreet Saini, Reetu Kundu, Manish Rohilla, Parikshaa Gupta, Nalini Gupta, Radhika Srinivasan, Uma Nahar Saikia, Pranab Dey
Cytojournal.2024; 21: 38. CrossRef
Morphometric study in thyroid tumors
Iuliana Mohorea, Bogdan Socea, Alexandru Carâp, Dragoș Șerban, Zenaida Ceaușu, Mihail Ceaușu
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef
The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong
Journal of Pathology and Translational Medicine.2018; 52(6): 404. CrossRef

Letter to the Editor

Myxoid Solitary Fibrous Tumor of the Central Nervous System: Haeri Han, Sangjeong Ahn, Won Hwangbo, Yang Seok Chae; Korean J Pathol. 2013;47(6):505-506. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.505

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Cervical Myxoid Solitary Fibrous Tumor: Report of an Unusual Variant and a Brief Overview of the Literature
Bingcheng Wu, Sok Yan Tay, Fredrik Petersson
Head and Neck Pathology.2020; 14(3): 852. CrossRef

Original Articles

Expression of Hepatocyte Growth Factor/c-met by RT-PCR in Meningiomas.: Na Rae Kim, Yang Seok Chae, Weon Jeong Lim, Seong Jin Cho; Korean J Pathol. 2011;45(5):463-468.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.463

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Abstract PDF: BACKGROUND
Hepatocyte growth factor (HGF) is a potent mitogenic cytokine. C-met protein, which is known to be the HGF receptor has transmembrane tyrosine kinase activity and is encoded by the c-met oncogene. The HGF/c-met signaling pathway may play various roles in the carcinogenesis of various organs.
METHODS
We examined HGF and c-met mRNA expression by utilizing reverse transcription polymerase chain reaction on 40 surgically resected intracranial meningiomas (25 benign, 10 atypical, and 5 anaplastic cases).
RESULTS
An HGF overexpression was detected in 28%, 50%, and 80% of the benign, atypical and anaplastic meningiomas, respectively; a high expression of HGF or the coexpression of HGF/c-met was detected in the high grade meningiomas (the atypical and anaplastic cases, p=0.046, p=0.014). An HGF expression was statistically significant in the recurrent meningiomas (p=0.003), and HGF expression was significantly lower than c-met mRNA expression in benign meningiomas (p=0.034).
CONCLUSIONS
There was no correlation between histologic subtypes and HGF/c-met expression. Determination of HGF expression can be used as a molecular predictor for recurrence of meningioimas. These results suggest that HGF and c-met expression in meningiomas may be associated with anaplastic progression.

Effect of Selective Cyclooxygenase 2 Inhibitor in TCDD Pre-exposed Thyroid Papillary Carcinoma Cell Line.: Hae Sung Kim, Kwang Sung Ahn, Jeong Hyeon Lee, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim; Korean J Pathol. 2011;45(1):1-8.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.1

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Abstract PDF

BACKGROUND
Cyclooxygenase 2 (COX-2) is related to carcinogenesis and progression of cancer. COX-2 has been detected in thyroid cancer. This suggests that COX-2 inhibitor may be useful to control the growth of thyroid cancer cells as well as the progression of thyroid cancer. Tetrachlorodibenzodioxin (TCDD), acting as an inflammatory cytokine, directly induces the expression of COX-2. We examine whether TCDD controls the effect of COX-2 inhibitor on thyroid cancer cells.
METHODS
The effects of TCDD and celecoxib on thyroid papillary carcinoma cell line (SNU790) were examined using cell proliferation and fluorescence-activated cell sorting analysis. Western blot analysis was performed to determine the expressed COX-2 levels and the cell cycle-related proteins. The matrix metalloproteinase-2 (MMP-2) expression and gelatinolytic activity were examined using real time-polymerase chain reaction and zymography.
RESULTS
TCDD directly induced the growth of SNU790 and the expression of cyclin D1, cyclin A, cyclin E, p21 and COX-2. Celecoxib suppressed the growth of SNU790 and the expression of cyclin D1 and cyclin E. Celecoxib reduced the MMP-2 expression and the gelatinolytic activity, but those effects were decreased in the SNU790 by either pre-treatment with TCDD or co-treatment with TCDD and celecoxib.
CONCLUSIONS
Celocoxib effect is directly reduced depending on the exposure to TCDD. TCDD exposure should be considered in the treatment with Celecoxib.

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Histone H3 phosphorylation, immediate-early gene expression, and the nucleosomal response: a historical perspective1This article is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.
Shannon Healy, Protiti Khan, Shihua He, James R. Davie
Biochemistry and Cell Biology.2012; 90(1): 39. CrossRef

Case Report

Hepatoid Thymic Carcinoma: A Case Report.: Jeong Hyeon Lee, Hyunchul Kim, Yang Seok Chae, Nam Hee Won, Jong Sang Choi, Chul Hwan Kim; Korean J Pathol. 2009;43(6):562-565.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.562

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Abstract PDF: We report here on a rare case of hepatoid thymic carcinoma in a 34-year-old man. The patient complained of a high fever and headache, and a 6.6cm-sized anterior mediastinal mass was found on chest computed tomography (CT). There was no hepatic mass seen on abdominal CT. The resected mass consisted of epithelioid cells with abundant eosinophilic cytoplasm, pleomorphic vesicular nuclei and prominent nucleoli, and the mass was surrounded by thymic tissue. The tumor cells were immunopositive for cytokeratin 7, alpha-1-antitrypsin, hepatocyte staining, and epithelial membrane antigen, but they were negative for CD5, alpha-fetoprotein (AFP) and placental alkaline phosphatase, and this all led to a diagnosis of hepatoid thymic carcinoma rather than hepatoid yolk sac tumor. This entity should be included in the differential diagnosis of epithelioid thymic tumors.

Original Articles

Immunohistochemical Study for p53 and hsc70 in Transitional Cell Carcinoma of the Urinary Bladder: Correlation with Histologic Grade, Clinical Stage and DNA Ploidy Pattern.: Hyuni Cho, Sung Jin Cho, Han Kyeom Kim, Yang Seok Chae; Korean J Pathol. 1995;29(6):766-775.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the genitourinary tract in Korea and its prognosis is determined by the histologic grade and clinical stage present at initial diagnosis. Recently, an extensive search for a more objective and reproducible method to evaluate the proliferation activity of cancer cells has been done. The p53 gene is located on the short arm of the chromosome 17 and acts as a cancer suppressor gene. Mutant p53 gene induces malignant transformation. Recent studies reveal that the level of mutant p53 protein is elevated in some human tumor and many diverse transformed cell lines. Heat shock proteins(HSPs) are present constitutively in normal cells, where they play an important role in normal cell metabolism. In mammalian cells, they are induced by a variety of physical and chemical stimuli. A protein that belongs to the hsp70 family, called hsc70, is only slightly heat inducible and is found at a higher level in growing cells than in the resting cells. The mutant p53 protein binds with hsc70 and the p53-hsc70 complex has functional significance in the transforming capacity of the mutant p53. We investigated the correlation between the p53 and hsc70 by immunohistochemical methods and with better defined prognostic indicators such as histologic grade, clinical stage, and DNA ploidy pattern in 42 transitional cell carcinomas of the urinary bladder. The results are summarized as follows. p53 expression rate was higher in the DNA aneuploid group than in the DNA diploid group(p=0.061), but there was no significant difference in the histologic grade(p=0.861) or clinical stage(p=0.154). The higher the hsc70 expression rate was, the poorer the tumor differentiation(p=0.000) and the deeper the invasion(p=0.001). The aneuploid group showed a higher hsc70 expression rate than the diploid group(p=0.017). 27 of 42(64.3%) carcinomas showed positivity of both p53 and hsc70. Though statistically insignificant, their correlation showed a relatively low correlation coefficient (P=0.059). In conclusion, we suspect that p53 and hsc70 are closely correlated to each other by comparing the results of this immunohistochemical study, and hsc70 will be a useful prognostic marker in transitional cell carcinomas of the urinary bladder after sufficient follow up studies are performed.

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Expression of p53 and Matrix Metalloproteinase-2 Proteins in Colorectal Adenocarcinoma.: Seong Jin Cho, Hwa Eun Oh, Yang Seok Chae; Korean J Pathol. 2000;34(7):494-500.

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Abstract PDF: The p53 gene is believed to play an important role through the mutation and overexpression in the progression of various human malignant tumors. The type IV collagenase (matrix metalloproteinase: MMP-2) initiates the degradation of the extracellular matrix, and consequently may play a role in the tumor invasion and metastasis. To investigate the correlation between clinicopathologic features of the colorectal adenocarcinomas and benign tumors and expression of p53 and MMP-2 proteins, we performed an immunohistochemical study on 40 colorectal adenocarcinomas, 20 adenomas and 20 hyperplastic polyps by using the antibodies to p53 and MMP-2 proteins. The positive expression rate of the p53 protein in adenocarcinomas was 62.5% and significantly higher than in benign tumors. The positive expression rate of the MMP-2 protein was 47.5% in adenocarcinomas, but there was no expression of MMP-2 protein in benign tumors. The difference in p53 and MMP-2 expression rates between malignant and non-malignant tumors was statistically significant. The positive expression rate of p53 protein in the non-metastatic and metastatic adenocarcinomas was 59.1 and 66.7%, respectively. The positive expression rate of MMP-2 protein in the non-metastatic and metastatic adencarcinomas was 45.5 and 50.0%, respectively. The correlation between several clinicopathologic features and expression of p53 and MMP-2 protein was not statistically significant, but the rate of positive MMP-2 immunoreactivity showed a statistically significant difference between Astler-Coller stage B1 C1 group and B2 C2 group of adenocarcinoma (p=0.0431). We concluded that the expression of p53 and MMP-2 protein contributes to the cancer development and MMP-2 may play a certain role in the invasiveness of the colorectal tumor. p53 and MMP-2 protein expression is not correlated with lymph node metastasis.

SPARC Expression in Thyroid Follicular Adenomas and Carcinomas.: Chung Yeul Kim, Seong Jin Cho, Min Kyung Kim, Yang Seok Chae; Korean J Pathol. 2000;34(12):1016-1021.

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Abstract PDF: SPARC, secreted protein acidic and rich in cysteine, is a extracellular matrix-associated protein implicated in the modulation of cell adhesion, migration, cell cycle regulation, and angiogenesis. SPARC is expressed in fibrocytes and endothelial cells involved in tissue repair and invasive malignant tumors in the gastrointestinal tract, breast, lung, kidney, adrenal cortex, ovary, and brain. This study was aimed to characterize the different expression of SPARC in the thyroid follicular adenomas and follicular carcinomas. Immunohistochemical staining was performed in paraffin-embedded tissues of 25 follicular adenomas and 15 follicular carcinomas of the thyroid gland. Immunohistochemically, SPARC was not expressed in the 19 follicular adenoma and 2 follicular carcinoma but highly expressed in the 6 follicular adenoma and 13 follicular carcinoma. These findings suggest that SPARC is a potential diagnostic marker of follicular carcinoma and is helpful to distinguish follicular carcinoma from follicular adenoma without vascular or capsular invasion.

Case Reports

Cytodiagnosis of Primary Small Cell Carcinoma of the Urinary Bladder: A Case Report.: Hye Sun Kim, Aee Ree Kim, Chul Hwan Kim, Yang Seok Chae, Nam Hee Won; Korean J Cytopathol. 1994;5(2):167-171.

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Abstract PDF: Samll cell carcinoma of the urinary bladder is a rare tumor which occurs in about 0.48% of all bladder tumors. We report cytologic features of small cell carcinoma of the urinary bladder in a 66-year-old man who had painless total gross hematuria, which was confirmed by partial cystectomy. In urine cytology, abundant tumor cells appeared in scattered and clustered forms in a bloody background. The tumor cells were small and uniform in size with a high nuclear/cytoplasmic ratio. The nuclei of the tumor cells were hyperchromatic, characteristically molded and showed inconspicuous nucleoli. The cytoplasms were scanty and plae blue.

Cytologic Features of Medullary Carcinoma of the Thyroid Occurring in a Child: A Case Report.: Jeong Seok Moon, Hye Sun Kim, Seong Jin Cho, Yang Seok Chae, Bom Woo Yeom; Korean J Cytopathol. 1996;7(2):213-217.

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Abstract PDF: Medullary carcinoma of the thyroid gland is a malignant neuroendocrine tumor arising from calcitonin producing-parafollicular cells. The tumor is clinically divided into sporadic and familial form, constituting about 80% and 20%, respectively. Recently, we experienced a case of unilateral and solitary sporadic medullary carcinoma of the left thyroid gland. The patient was a 9 year-old female, who presented with a palpable mass on the anterior lateral neck of 8 months duration without any familial and personal history of neuroendocrine disease. The cytopathologic findings showed spindle cells and plasmacytoid cells in the background of colloid-like materal. The nuclei were eccentrically located, mildly hyperchromatic and pleomorphic, showing speckled chromatin pattern without nuclear inclusion or prominent nucleoli. The cytoplasm was abundant and had a pale granular cyanophilic appearance. No amyloid materal could be identified.

Sinonasal Undifferentiated Carcinoma: A Case Report .: Mi Kyung Shin, Yang Seok Chae; Korean J Cytopathol. 1997;8(1):98-102.

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Abstract PDF: Sinonasal undifferentiated carcinoma(SNUC) is a distinct, relatively rare neoplasm arising in the nasal cavity and paranasal sinuses composed of undifferentiated epithelial cells and clinically characterized by a fulminant course. We report a case of SNUC in a 56-year old man who have had bilateral neck masses since one month ago before coming to our hospital. The paranasal computed tomography showed soft mass density in the left maxillary sinus and the nasal cavity with bone destruction in the anterior medial and the inferior maxillary sinus wall. This mass was extruded into the left orbital wall. Biopsy of the nasal mass and fine needle aspiration(FNA) of the neck mass were done. FNA revealed medium-sized neoplastic cells forming clusters or individually dispersed. Nuclei were round to oval, slightly to moderately pleomorphic, and hyperchromatic. Chromatin was finely granular, but occasionally was coarsely granular. Nucleoli varied from large to inconspicuous and the cytoplasm was scanty.

Metastatic Germinoma of Spleen from Perichiasmal Area: A Case Report .: Bong Kyung Shin, Min Kyung Kim, Han Kyeom Kim, Yang Seok Chae, Nam Hee Won, Insun Kim; Korean J Cytopathol. 2001;12(1):61-65.

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Abstract PDF: A 20-year-old young man who had undergone treatment for a suprasellar/perichiasmal tumor 2 years before, was presented with a huge palpable splenic mass. A fine needle aspiration cytology from the splenic mass showed dissociated large pleomorphic tumor cells having irregular nuclear outline, coarse chromatin, and one or two macronucleoli, and scattered small lymphocytes in fine granular background. Above cytologic findings were regarded as the characteristics of germinoma. Differential diagnosis from the large cell lymphoma of spleen was emphasized.

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